CD4+Foxp3+ regulatory T cells in the control of autoimmunity: in vivo veritas.
The immune system requires a homeostatic equilibrium between the mechanisms that assure self-tolerance, those that control the capacity to mount life-long immunity to pathogenic microbes, and those that attenuate effector mechanisms from inducing immune pathology [Sakaguchi S, Yamaguchi T, Nomura T, Ono M: Regulatory T cells and immune tolerance. Cell 2008, 133 (5):775-87; Piccirillo CA, Thornton AM: Cornerstone of peripheral tolerance: naturally occurring CD4+CD25+regulatory T cells. Trends Immunol 2004, 25:374-80]. In the past decade, an overwhelming body of literature showed that CD4+Foxp3+ regulatory T (Treg) cells are a dominant mechanism regulating the decision fate of these different immunological outcomes. Indeed, CD4+Foxp3+ Treg cells develop largely in the thymus but can be induced in the periphery throughout the course of immune responses [Sakaguchi S, Yamaguchi T, Nomura T, Ono M: Regulatory T cells and immune tolerance. Cell 2008, 133 (5):775-87; Piccirillo CA, Thornton AM: Cornerstone of peripheral tolerance: naturally occurring CD4+CD25+regulatory T cells. Trends Immunol 2004, 25:374-80]. Treg cells have emerged as a central control point in the regulation of autoimmune responses. Despite progress made in various in vitro and in vivo models, much uncertainty exists over their mechanism of action in vivo. Here, we summarize research characterizing the functional dynamics of CD4+Foxp3+ Treg cells in the control of autoimmunity in rodents and humans.
Piccirillo
Ciriaco A
CA
Department of Microbiology and Immunology, and Center for the Study of Host Resistance, McGill University and the Research Institute of the McGill University Health Center, Montreal, QC, Canada H3A 2B4. Ciro.piccirillo@mcgill.ca
d'Hennezel
Eva
E
Sgouroudis
Evridiki
E
Yurchenko
Ekaterina
E
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors